(S) or L-3-(3,4-Dihydroxyphenyl)alanine, more commonly known as L-dopa or levodopa and represented by the formula ##STR1## is a drug useful in the treatment of Parkinson's disease, Merck Index, Tenth Edition, pp. 784-5. The substance may be produced from natural materials such as Vicia Faba beans, U.S. Pat. No. 3,253,023, by fermentation of L-tyrosine, J. Am. Chem. Soc. 91, 6204 (1969) and by various synthetic methods. Synthetic methods include chemical asymmetric synthesis, enzymatic asymmetric synthesis and resolution methods.
In U.S. Pat. No. 4,005,127 is described a chemical asymmetric synthesis which includes the step in which the racemic mixture of a precursor compound, .alpha.-acetamido-4-hydroxy-3-methoxycinnamic acid acetate is hydrogenated in the presence of a catalyst mixture of a metal coordination complex in combination with an optically active phosphine or arsine ligand to produce the L-enantiomer of N-acetyl-3-(4-hydroxy-3-methoxyphenyl)-alanine acetate. Another asymmetric synthesis is that described by L. N. Kaigorodova et al, in Izvestiya Okal. Nauk SSSR, 5, 1090, an asymmetric reductive aminolysis of m-methoxy-p-acetoxy-.alpha.-acetamidocinnamic acid azlactone in the presence of S-.alpha.-phenylethylamine and palladium catalyst to produce an SS-diastereomer of m-methoxy-p-acetoxy-N-acetylphenylalanine-.alpha.-phenylethylamide which after crystallization and hydrolysis produced pure L-dopa.
Resolution methods include the traditional method of treating a racemic mixture with an optically active material to form derivatives and thereafter physically separating the derivatives, and the kinetic crystallization technique where one isomer of the racemic mixture preferentially crystallizes. A number of the latter type which have been carried out in the laboratory are listed in Chemical Reviews, 80, 228 (1980).
Many of the reported literature methods are not adaptable as a synthetic method suitable for preparing commercial quantities of L-dopa because of slowness of reaction, difficulty of the separation step or difficulty in recycling the unwanted isomer. Moreover, some of the reported require hazardous or potentially hazardous materials and/or large volumes of organic solvents.